Task force advice against thyroid cancer screening ‘appropriate and timely’

Megan R. Haymart
Karina W. Davidson

The U.S. Preventive Services Task Force’s final recommendation against thyroid cancer screening in asymptomatic adults reflects increasing concerns about overdiagnosis and overtreatment, according to leaders in the field.

The D recommendation — the same grade the U.S. Preventive Services Task Force (USPSTF) issued for thyroid cancer screening in 1996 — indicates there is moderate or high certainty that screening has no net benefit, or that the harms of screening outweigh the benefits.

“The USPSTF recommendation against screening for thyroid cancer in adults without signs or symptoms of the disease is an appropriate and timely recommendation,” Megan R. Haymart, MD, assistant professor of medicine at University of Michigan Health System, told Endocrine Today. “Screening for thyroid cancer will lead to more detection of disease. However, on thorough autopsy studies, close to one-third of adults who die of other causes have small thyroid cancers. For most adults, these small thyroid cancers never go on to cause harm.”

Thyroid cancer incidence increased by 4.5% per year in the past 10 years, a rate higher than for any other cancer. Incidence climbed from 4.9 cases per 100,000 individuals in 1975 to 15.3 cases per 100,000 in 2013.

SEER data indicate approximately 637,115 individuals in the United States had thyroid cancer in 2013. An estimated 56,870 new cases will be diagnosed this year, accounting for 3.4% of all new cancer cases in the country.

Despite increased incidence, thyroid cancer mortality has remained relatively unchanged. Five-year overall survival is 98.1% for all patients, 99.9% for those with localized disease and 55.3% for those with distant disease.

“We have no direct evidence to determine the rate of overdiagnosis that may be occurring in the United States, but we have indirect evidence that we have an increasing rate of detection of thyroid cancer,” task force member Karina W. Davidson, PhD, MASc, professor in the departments of medicine, cardiology and psychiatry at Columbia University Medical Center, told Endocrine Today. “Even though most of those are treated, we don’t have a change in longevity, and that can speak indirectly to the possibility of overdiagnosis.

“Our evidence review suggested that thyroid cancer is rare in the United States, and there were very few benefits to screening adults with no symptoms or signs,” Davidson added. “We did find in our review serious harms associated with surgery, particularly for those who had small tumors, and for these reasons we are advising against screening patients with no symptoms or signs.”

Among adults without symptoms or signs of thyroid cancer, most lesions are benign and slow growing and will not affect the person’s health, Davidson said.

“Yet, once told that someone has cancer, the immediate impulse is to assume that surgery or treatment is the best way of dealing with it,” she said. “It is hard for people to understand that screening can sometimes be a bad thing but, in this case, it is leading to harms from surgery. We do not see that it is benefitting longevity or quality of life.”

Screening harms

The USPSTF last issued a thyroid cancer screening recommendation in 1996.

To update that recommendation, the task force commissioned a systematic evidence review to examine the benefits and harms of screening for thyroid cancer in asymptomatic adults. The task force also assessed the diagnostic accuracy of screening — including through neck palpation and ultrasound — and the benefits and harms associated with treatment of screen-detected thyroid cancer.

“Once you’ve been screened and told you have something that might be cancer, the trajectory toward either radiation or surgery is highly likely,” Davidson said. “Harms can include damage to the nerves that control speaking and damage to the parathyroid gland functions, along with hypoparathyroidism.”

Jennifer S. Lin

During the systematic review, Jennifer S. Lin, MD, MCR, director of Evidence-based Practice Center at Kaiser Permanente Center for Health Research, and colleagues evaluated evidence from 67 studies published from 1966 to January 2016.

Based on 36 fair-quality studies (n = 43,295) that reported on harms associated with thyroid surgery and radioactive iodine therapy, researchers found the rate of permanent hypoparathyroidism varied greatly, from 2.12 to 5.93 events per 100 thyroidectomies. Researchers estimated a rate of 0.99 to 2.13 events of permanent recurrent laryngeal nerve palsy per 100 surgeries, with or without lymph node dissection.

Based on 16 studies (n = 291,796), treatment of differentiated thyroid cancer with radioactive iodine increased risk for permanent adverse effects on the salivary gland — such as dry mouth — and slightly increased risk for second primary malignancies.

“Treatment of thyroid cancer is associated with surgical risks — including permanent voice changes and low calcium — and with risks from radioactive iodine, including salivary gland damage and lacrimal duct damage,” Haymart, an Endocrine Today Editorial Board member, said. “Most patients with thyroid cancer have relatively indolent disease and, although there are a small proportion of patients with aggressive and deadly disease, there is no evidence that screening the population at large improves outcomes for this small subset.”

Overall, the task force found inadequate evidence to estimate the accuracy of neck palpation or ultrasound as a screening test.

One prospective study (n = 253) conducted by researchers in Finland showed 5.1% of randomly selected adults had abnormal findings (thyroid nodule or diffuse enlargement) on neck examination. Researchers reported a sensitivity to detect thyroid nodules of 11.6% (95% CI, 5.1-21.6) and specificity of 97.3% (95% CI, 93.8-99.1).

A prospective, population-based study (n = 2,079) conducted in South Korea reported on diagnostic accuracy of ultrasound screening. Results showed a 94.3% (95% CI, 84.3-98.8) sensitivity and 55% (95% CI, 41.6-68.9) specificity.

Lin and colleagues concluded that, although ultrasonography of the neck using high-risk sonographic characteristics plus follow-up cytology from fine-needle aspiration can identify thyroid cancers, it is unclear if population-based or targeted screening can decrease mortality rates or improve patient outcomes.

“The bottom line is, we don’t have trials or well-designed observational studies to support screening for thyroid cancer,” Lin told Endocrine Today. “Studies using SEER data suggest that if you are diagnosed with papillary thyroid cancer in the United States, you almost certainly will be treated, meaning having your thyroid or part of your thyroid removed.

“Although thyroidectomies are generally safe, they are not without potential complications,” Lin added. “The biggest problem is that we don’t yet have a good way to determine which papillary thyroid cancers need to be treated; that is, which of these cancers will actually cause harm to the patient. Survival data from SEER, ecological data and autopsy data suggest that many papillary thyroid cancers don’t need to be treated.”

The USPSTF’s recommendation against screening does not apply to individuals with hoarseness, pain, difficulty swallowing or other throat symptoms, or those who have lumps, swelling, asymmetry of the neck or other reasons for examination. It also does not apply to individuals at increased risk for thyroid cancer because of a history of exposure to ionizing radiation — either through medical treatment or radiation fallout — diets low in iodine, an inherited genetic syndrome associated with thyroid cancer, or a first-degree relative with a history of thyroid cancer.

“Certainly, for people who have a personal childhood history of irradiation or a family history of thyroid cancer, they may want to speak to their clinician about individualizing the decision to be screened,” Davidson said.

Research needs

Researchers found no studies that compared patient health outcomes for screened vs. unscreened individuals to assess the effectiveness of early detection and treatment.

However, one fair-quality retrospective observational study used SEER data from 1973 to 2005 to compare survival rates of individuals treated (n = 35,663) vs. not treated (n = 440) for papillary thyroid cancer.

Results showed a slightly worse 20-year survival rate among untreated individuals than treated patients (97% vs. 99%; P < .001). However, researchers did not adjust for potential confounding, despite statistically significant baseline differences between the two groups.

“Given the very real concern about overdiagnosis and subsequent overtreatment, it is important to conduct screening trials or good-quality observational studies in populations at risk for thyroid cancer,” Lin said. “We also need trials or well-designed observational studies of early treatment vs. surveillance of papillary thyroid cancers. Most importantly, we need research to identify and vet prognostic indicators — either tumor makers or patient risk predictors — that can predict indolent aggressive vs. indolent thyroid cancer.”

There is a “research gap” in the area of active surveillance, Davidson said.

“We do not have evidence to suggest that watchful waiting is appropriate, and we do not have evidence that we can differentiate the small-growing tumors from those that are dangerous,” Davidson said. “Clearly, research is needed on both of those areas to help us guide oncologists about the appropriate treatments.

“We can suggest that any ways to reduce unnecessary radiation to the neck and throat is one way to prevent thyroid cancer,” Davidson added. “We have no recommendation at this point for patients who have symptoms or signs of thyroid cancer. We need more research for those patients to know what the best course of treatment is for them.”

Anne R. Cappola

In addition, there is a lack of knowledge about the differences between a thyroid cancer that never leaves the capsule of its nodule and a thyroid cancer that does, either through local extension or distant metastasis, Anne R. Cappola, MD, ScM, professor of medicine in the division of endocrinology, diabetes and metabolism at Perelman School of Medicine at University of Pennsylvania, wrote in an editorial that accompanied the task force’s recommendation.

“The prognosis of each thyroid nodule, prior to surgical excision, is needed,” Cappola wrote. “Perhaps the difference between thyroid nodules that require surgery and those that do not involves the characteristics of the patient, not the characteristics of the nodule. Perhaps the difference is in immune surveillance or some other aspect of the patient, and one patient can keep the thyroid cancer contained to the nodule and another cannot.

Julie Ann Sosa

“Using the same tools — palpation, ultrasound imaging and findings on microscopic examination — is unlikely to result in a different conclusion about screening for thyroid cancer in the future,” Cappola added. “New technologies are required.”

However, the steadily increasing incidence of thyroid cancer should prompt researchers to investigate other explanations beyond overdiagnosis, such as obesity or environmental factors, Julie Ann Sosa, MD, MA, chief of endocrine surgery at Duke University, and colleagues wrote in another editorial.

Thyroid cancer linked to radiation exposure has declined — based on prevalence of RET proto-oncogene chromosomal aberrations — whereas BRAF V600E mutation prevalence has increased. This suggests an increasing role in chemical exposure.

“The indications for adjuvant radioactive iodine are fewer, and recommended doses of iodine 131 have decreased,” Sosa and colleagues wrote. “If the explanation for the rise in thyroid cancer is, indeed, not just overdiagnosis, and if mortality from thyroid cancer is also increasing, then enthusiasm for this (non)screening recommendation should be more muted.

“For clinicians and scientists working in the field of thyroidology, this is an interesting and compelling time,” Sosa and colleagues added. “Clearly, more research is needed to identify alternative causes for the increasing incidence of the disease, to inform efforts at prevention, and to develop novel approaches to the management of advanced thyroid cancer.” – by Chuck Gormley

Disclosure: The researchers report no relevant financial disclosures. Cappola reports no relevant financial disclosures. Sosa reports serving on the data monitoring committee of the Medullary Thyroid Cancer Consortium Registry supported by AstraZeneca, Eli Lilly, Glaxo SmithKline and NovoNordisk. The other editorial authors report no relevant financial disclosures.

Megan R. Haymart
Karina W. Davidson

The U.S. Preventive Services Task Force’s final recommendation against thyroid cancer screening in asymptomatic adults reflects increasing concerns about overdiagnosis and overtreatment, according to leaders in the field.

The D recommendation — the same grade the U.S. Preventive Services Task Force (USPSTF) issued for thyroid cancer screening in 1996 — indicates there is moderate or high certainty that screening has no net benefit, or that the harms of screening outweigh the benefits.

“The USPSTF recommendation against screening for thyroid cancer in adults without signs or symptoms of the disease is an appropriate and timely recommendation,” Megan R. Haymart, MD, assistant professor of medicine at University of Michigan Health System, told Endocrine Today. “Screening for thyroid cancer will lead to more detection of disease. However, on thorough autopsy studies, close to one-third of adults who die of other causes have small thyroid cancers. For most adults, these small thyroid cancers never go on to cause harm.”

Thyroid cancer incidence increased by 4.5% per year in the past 10 years, a rate higher than for any other cancer. Incidence climbed from 4.9 cases per 100,000 individuals in 1975 to 15.3 cases per 100,000 in 2013.

SEER data indicate approximately 637,115 individuals in the United States had thyroid cancer in 2013. An estimated 56,870 new cases will be diagnosed this year, accounting for 3.4% of all new cancer cases in the country.

Despite increased incidence, thyroid cancer mortality has remained relatively unchanged. Five-year overall survival is 98.1% for all patients, 99.9% for those with localized disease and 55.3% for those with distant disease.

“We have no direct evidence to determine the rate of overdiagnosis that may be occurring in the United States, but we have indirect evidence that we have an increasing rate of detection of thyroid cancer,” task force member Karina W. Davidson, PhD, MASc, professor in the departments of medicine, cardiology and psychiatry at Columbia University Medical Center, told Endocrine Today. “Even though most of those are treated, we don’t have a change in longevity, and that can speak indirectly to the possibility of overdiagnosis.

“Our evidence review suggested that thyroid cancer is rare in the United States, and there were very few benefits to screening adults with no symptoms or signs,” Davidson added. “We did find in our review serious harms associated with surgery, particularly for those who had small tumors, and for these reasons we are advising against screening patients with no symptoms or signs.”

PAGE BREAK

Among adults without symptoms or signs of thyroid cancer, most lesions are benign and slow growing and will not affect the person’s health, Davidson said.

“Yet, once told that someone has cancer, the immediate impulse is to assume that surgery or treatment is the best way of dealing with it,” she said. “It is hard for people to understand that screening can sometimes be a bad thing but, in this case, it is leading to harms from surgery. We do not see that it is benefitting longevity or quality of life.”

Screening harms

The USPSTF last issued a thyroid cancer screening recommendation in 1996.

To update that recommendation, the task force commissioned a systematic evidence review to examine the benefits and harms of screening for thyroid cancer in asymptomatic adults. The task force also assessed the diagnostic accuracy of screening — including through neck palpation and ultrasound — and the benefits and harms associated with treatment of screen-detected thyroid cancer.

“Once you’ve been screened and told you have something that might be cancer, the trajectory toward either radiation or surgery is highly likely,” Davidson said. “Harms can include damage to the nerves that control speaking and damage to the parathyroid gland functions, along with hypoparathyroidism.”

Jennifer S. Lin

During the systematic review, Jennifer S. Lin, MD, MCR, director of Evidence-based Practice Center at Kaiser Permanente Center for Health Research, and colleagues evaluated evidence from 67 studies published from 1966 to January 2016.

Based on 36 fair-quality studies (n = 43,295) that reported on harms associated with thyroid surgery and radioactive iodine therapy, researchers found the rate of permanent hypoparathyroidism varied greatly, from 2.12 to 5.93 events per 100 thyroidectomies. Researchers estimated a rate of 0.99 to 2.13 events of permanent recurrent laryngeal nerve palsy per 100 surgeries, with or without lymph node dissection.

Based on 16 studies (n = 291,796), treatment of differentiated thyroid cancer with radioactive iodine increased risk for permanent adverse effects on the salivary gland — such as dry mouth — and slightly increased risk for second primary malignancies.

“Treatment of thyroid cancer is associated with surgical risks — including permanent voice changes and low calcium — and with risks from radioactive iodine, including salivary gland damage and lacrimal duct damage,” Haymart, an Endocrine Today Editorial Board member, said. “Most patients with thyroid cancer have relatively indolent disease and, although there are a small proportion of patients with aggressive and deadly disease, there is no evidence that screening the population at large improves outcomes for this small subset.”

PAGE BREAK

Overall, the task force found inadequate evidence to estimate the accuracy of neck palpation or ultrasound as a screening test.

One prospective study (n = 253) conducted by researchers in Finland showed 5.1% of randomly selected adults had abnormal findings (thyroid nodule or diffuse enlargement) on neck examination. Researchers reported a sensitivity to detect thyroid nodules of 11.6% (95% CI, 5.1-21.6) and specificity of 97.3% (95% CI, 93.8-99.1).

A prospective, population-based study (n = 2,079) conducted in South Korea reported on diagnostic accuracy of ultrasound screening. Results showed a 94.3% (95% CI, 84.3-98.8) sensitivity and 55% (95% CI, 41.6-68.9) specificity.

Lin and colleagues concluded that, although ultrasonography of the neck using high-risk sonographic characteristics plus follow-up cytology from fine-needle aspiration can identify thyroid cancers, it is unclear if population-based or targeted screening can decrease mortality rates or improve patient outcomes.

“The bottom line is, we don’t have trials or well-designed observational studies to support screening for thyroid cancer,” Lin told Endocrine Today. “Studies using SEER data suggest that if you are diagnosed with papillary thyroid cancer in the United States, you almost certainly will be treated, meaning having your thyroid or part of your thyroid removed.

“Although thyroidectomies are generally safe, they are not without potential complications,” Lin added. “The biggest problem is that we don’t yet have a good way to determine which papillary thyroid cancers need to be treated; that is, which of these cancers will actually cause harm to the patient. Survival data from SEER, ecological data and autopsy data suggest that many papillary thyroid cancers don’t need to be treated.”

The USPSTF’s recommendation against screening does not apply to individuals with hoarseness, pain, difficulty swallowing or other throat symptoms, or those who have lumps, swelling, asymmetry of the neck or other reasons for examination. It also does not apply to individuals at increased risk for thyroid cancer because of a history of exposure to ionizing radiation — either through medical treatment or radiation fallout — diets low in iodine, an inherited genetic syndrome associated with thyroid cancer, or a first-degree relative with a history of thyroid cancer.

“Certainly, for people who have a personal childhood history of irradiation or a family history of thyroid cancer, they may want to speak to their clinician about individualizing the decision to be screened,” Davidson said.

Research needs

Researchers found no studies that compared patient health outcomes for screened vs. unscreened individuals to assess the effectiveness of early detection and treatment.

PAGE BREAK

However, one fair-quality retrospective observational study used SEER data from 1973 to 2005 to compare survival rates of individuals treated (n = 35,663) vs. not treated (n = 440) for papillary thyroid cancer.

Results showed a slightly worse 20-year survival rate among untreated individuals than treated patients (97% vs. 99%; P < .001). However, researchers did not adjust for potential confounding, despite statistically significant baseline differences between the two groups.

“Given the very real concern about overdiagnosis and subsequent overtreatment, it is important to conduct screening trials or good-quality observational studies in populations at risk for thyroid cancer,” Lin said. “We also need trials or well-designed observational studies of early treatment vs. surveillance of papillary thyroid cancers. Most importantly, we need research to identify and vet prognostic indicators — either tumor makers or patient risk predictors — that can predict indolent aggressive vs. indolent thyroid cancer.”

There is a “research gap” in the area of active surveillance, Davidson said.

“We do not have evidence to suggest that watchful waiting is appropriate, and we do not have evidence that we can differentiate the small-growing tumors from those that are dangerous,” Davidson said. “Clearly, research is needed on both of those areas to help us guide oncologists about the appropriate treatments.

“We can suggest that any ways to reduce unnecessary radiation to the neck and throat is one way to prevent thyroid cancer,” Davidson added. “We have no recommendation at this point for patients who have symptoms or signs of thyroid cancer. We need more research for those patients to know what the best course of treatment is for them.”

Anne R. Cappola

In addition, there is a lack of knowledge about the differences between a thyroid cancer that never leaves the capsule of its nodule and a thyroid cancer that does, either through local extension or distant metastasis, Anne R. Cappola, MD, ScM, professor of medicine in the division of endocrinology, diabetes and metabolism at Perelman School of Medicine at University of Pennsylvania, wrote in an editorial that accompanied the task force’s recommendation.

“The prognosis of each thyroid nodule, prior to surgical excision, is needed,” Cappola wrote. “Perhaps the difference between thyroid nodules that require surgery and those that do not involves the characteristics of the patient, not the characteristics of the nodule. Perhaps the difference is in immune surveillance or some other aspect of the patient, and one patient can keep the thyroid cancer contained to the nodule and another cannot.

PAGE BREAK
Julie Ann Sosa

“Using the same tools — palpation, ultrasound imaging and findings on microscopic examination — is unlikely to result in a different conclusion about screening for thyroid cancer in the future,” Cappola added. “New technologies are required.”

However, the steadily increasing incidence of thyroid cancer should prompt researchers to investigate other explanations beyond overdiagnosis, such as obesity or environmental factors, Julie Ann Sosa, MD, MA, chief of endocrine surgery at Duke University, and colleagues wrote in another editorial.

Thyroid cancer linked to radiation exposure has declined — based on prevalence of RET proto-oncogene chromosomal aberrations — whereas BRAF V600E mutation prevalence has increased. This suggests an increasing role in chemical exposure.

“The indications for adjuvant radioactive iodine are fewer, and recommended doses of iodine 131 have decreased,” Sosa and colleagues wrote. “If the explanation for the rise in thyroid cancer is, indeed, not just overdiagnosis, and if mortality from thyroid cancer is also increasing, then enthusiasm for this (non)screening recommendation should be more muted.

“For clinicians and scientists working in the field of thyroidology, this is an interesting and compelling time,” Sosa and colleagues added. “Clearly, more research is needed to identify alternative causes for the increasing incidence of the disease, to inform efforts at prevention, and to develop novel approaches to the management of advanced thyroid cancer.” – by Chuck Gormley

Disclosure: The researchers report no relevant financial disclosures. Cappola reports no relevant financial disclosures. Sosa reports serving on the data monitoring committee of the Medullary Thyroid Cancer Consortium Registry supported by AstraZeneca, Eli Lilly, Glaxo SmithKline and NovoNordisk. The other editorial authors report no relevant financial disclosures.